. The objective of this FIRST award in epidemiology is to examine the role of several commonly used medications that may either increase (hormones, antidepressants) or decrease (nonsteroidal anti-inflammatory drugs (NSAIDs), anti-oxidants) the risk of breast cancer. The proposed studies will utilize the infrastructure established for a large, population-based, case-control study of breast cancer in North Carolina, the Carolina Breast Cancer Study (CBCS). The CBCS will have enrolled 800 cases and 800 controls by the end of its first phase in spring, 1996, and an additional 1600 participants will be recruited in its second phase. The study population will have approximately equal numbers of black and white women, allowing an evaluation of potential racial differences in the association of these medications and breast cancer risk. Information on hormone use and anti-oxidant consumption is currently being collected as part of a comprehensive questionnaire on breast cancer risk factors. Questions to assess the use of NSAIDs and antidepressants will be developed and added to the questionnaire used in the second phase of the CBCS. Analyses of the data will focus on hypotheses derived from preliminary investigations, including animal studies (i.e., NSAIDs' protective effect, and the antidepressants' tumor promotion effect) or questions that have remained unanswered due to temporal considerations (i.e., the risk of peri- and postmenopausal breast cancer among women who used oral contraceptives early in their reproductive years, and the risk among women who used both oral contraceptives and menopausal hormones). The investigation of the roles these medications play in the development of breast cancer is important for several reasons. Physicians and patients should know the potential adverse effects associated with a given therapy so they can make informed judgments of the benefits versus the risks. Because millions of women are prescribed hormones and antidepressants each year, even a model increase in risk could translate into a large number of breast cancers. For the medications with evidence suggestive of a protect effect, it is important.